Strong evidence has been found for the existence of a nitrogen catabolic enzyme (NCE) system that involves the regulation of a group of liver enzymes functioning in nitrogen catabolism and excretion. We know that xanthine dehydrogenase (XDH), purine nucleoside phosphorylase, tyrosine aminotransferase and tryptophan pyrrolase (TP) are regulated by a common mechanism and plan to survey other enzymes to ascertain the scope of this mechanism. It appears likely that melatonin is a principal element in this control system and that Schiff's bases between pyridoxal phosphate and amino acids are important agents. Agents acting directly on the liver will be identified using a liver slice system that retains the capacity to synthesize XDH subunits. In studying XDH synthesis and degradation in chicks and in liver slices, we have found compelling evidence that translation gives an inactive form of XDH (I1) that is converted to active enzyme (E). Furthermore, E must be converted to a second inactive form (I2) before it can be degraded. We plan to study each intermediate and process in detail so that post-transcriptional events (activation, degradation, etc.) subject to regulation can be identified. TP will be studied in a similar way and compared with the XDH system to identify any general characteristics. We plan to study regulation of XDH and other nitrogen catabolic enzymes in the pancreas. We know that pancreatic XDH is controlled by dietary carbohydrate rather than protein. Since XDH seems to be identical from these two tissues, a comparison of the two distinct regulatory systems should be interesting from both the physiological and differentiation points of view. BIBLIOGRAPHIC REFERENCES: Woodward, W.D. and Fisher, J.R. (1976). A Possible Role for Melatonin in Regulation of Chick Liver Xanthine Dehydrogenase Activity. Arch. Biochem. Biophys. 173, 389-391. Fisher, J.R., Stewart, T.A., Wu, J.M., Nickels, J.S. and High, J.A. (1976). Regulation of Nitrogen Catabolic Enzymes in Chick Liver - Effects of Amino Acids. Enzyme (in press).